title: Calyxin Y induces hydrogen peroxide-dependent autophagy and apoptosis via JNK activation in human non-small cell lung cancer NCI-H460 cells.
abstract: Calyxin Y has been recently isolated from Alpinia katsumadai which has a folk use as an anti-tumor medicine. Calyxin Y induced caspase-dependent cell death in NCI-H460 cells, and concomitantly, provoked cytoprotective autophagy with the upregulation of critical Atg proteins. The cleavage of Atg proteins by caspases acted as a switch between autophagy and apoptosis induced by calyxin Y. Intracellular hydrogen peroxide (H2O2) production was triggered upon exposure to calyxin Y via the induction of autophagy and apoptosis. We provided evidence that activated JNK was upstream effectors controlling both autophagy and apoptosis in response to elevated H2O2. Therefore, our findings demonstrate that calyxin Y serves multiple roles as a promising chemotherapeutic agent that induces H2O2-dependent autophagy and apoptosis via JNK activation.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Xiao-bing
authors.initials: XB
authors.lastname: Wang
authors.forename: Jun-song
authors.initials: JS
authors.lastname: Wang
authors.forename: Ya-di
authors.initials: YD
authors.lastname: Geng
authors.forename: Chang-shui
authors.initials: CS
authors.lastname: Yang
authors.forename: Ling-yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D002289:Carcinoma, Non-Small-Cell Lung; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D053938:DNA Fragmentation; D036381:Diarylheptanoids / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C466624:ATG12 protein, human; C502778:ATG5 protein, human; D000972:Antineoplastic Agents, Phytogenic; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D047188:Chalcones; D036381:Diarylheptanoids; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C584445:calyxin Y; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases
keywords: 2′,7′-dichlorofluorescein-diacetate; Apoptosis; Atg; Atgs; Autophagy; BCA; BSA; Calyxin Y; DCF; DCFH-DA; ECL; ERK; JNK; LC3; MAPK; PI; ROS; SDS–PAGE; TBST; autophagy related genes; bicinchoninic acid; c-Jun N-terminal protein kinases; dichlorofluorescein; enhanced chemiluminescence; extracellular signal-regulated kinases; fetal bovine serum albumin; microtubule-associated protein1 light chain 3; mitogen-activated protein kinase; propidium iodide; reactive oxygen species; sodium dodecyl sulfate–polyacrylamide gel electrophoresis; tris-buffered saline containing 0.1% Tween-20